The clusters are activated within the target pathology by diagnostic US, undergo an ensuing liquid-to-gas phase shift and transiently deposit 20 30 μm large bubbles in the microvasculature, occluding blood flow for ∼5 10 min.
We only pooled data from studies involving the exact same index test and target pathology.
This section discusses suitable target pathology and delivery method of this reagent, and studies necessary for the first-in-human study.
This is of particular importance in the heterogeneous MCI population, since inclusion of a significant proportion of individuals without amyloid pathology introduces noise into the clinical trial, and may expose individuals without the target pathology to needless risk.
Once the target pathology and the delivery mode of the ONO-1301SR treatment were decided, dose-optimisation study ideally using a large animal model is necessary to launch the clinical study.
Since several prostagrandin agonists are the standard treatment of primary and secondary PAH in the clinical practice [ 81, 82], an ideal target pathology of ONO-1301 and/or ONO-1301SR treatment might be PAH or associated lung diseases.
Although positive effects of ONO-1301SR treatment were proven on a variety of cardiac pathologies, such as acute MI, idiopathic dilated cardiomyopathy, ischaemic cardiomyopathy, cardiac allograft disease post-transplantation or fulminant myocarditis, it is a key of success of this treatment to optimise delivery method of ONO-1301 for each target pathology in clinical study.
Tissue-specific promoters, such as Pdx1-cre, are sometimes expressed in other tissues, resulting in off-target pathologies, such as papillomas and lymphoma.
The reductionist approach in medical research can yield only a limited understanding of complicated pathogenesis and multi-target pathologies of systemic diseases, and it has difficulty in identifying relevant interventions to target such complexities.
For example, mutant genes may be expressed in the entire pancreas through the use of embryonic pancreatic promoters such as Pdx-1 and p48 (Hingorani et al., 2003, 2005; Westphalen and Olive, 2012), but the leakiness of these promoters may result in off-target pathologies in other tissues (Gades et al., 2008; Hingorani et al., 2003, 2005).
